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Biomedical subjects

C Nichols

Publications and source records attributed to C Nichols.

At least 37 records · Page 2Linked to original sources

Dentistry and hypertension.

The author monitored the systolic and diastolic blood pressure, or BP; mean arterial pressure, or MAP; and heart rate, or HR, of hypertensive and normotensive patients once each minute during dental procedures. He found statistically significant differences in the means of the initial five and final five systolic BP and diastolic BP, MAP and HR readings. Exceptions were the HR in 18- to 45-year-old normotensive patients and the systolic BP in hypertensive patients. The author concluded that the time at which BP is monitored during a dental procedure may be significant.

Adolescent↗

2-Chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas.

In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.

Adult↗

Serum progesterone and human chorionic gonadotrophin measurements in the evaluation of ectopic pregnancy.

We evaluated the clinical usefulness of measuring the serum concentrations of human chorionic gonadotrophin (HCG) and progesterone to distinguish between early viable and nonviable pregnancies. We investigated 110 women with clinical symptoms of abnormal pregnancy. A single HCG measurement did not clearly distinguish between ectopic and failing intrauterine pregnancies; an HCG value below 3,000 IU/L, together with a serum progesterone below 40 nmol/L, predicted abnormal pregnancy outcome in 97% of women (positive predictive value: 91%; negative predictive value: 95%). Serum HCG value above 3,000 IU/L or progesterones above 40 nmol/L, discriminated between an ongoing pregnancy and an abnormal pregnancy in 87% women (positive predictive value: 95%; negative predictive value: 91%) and provided reassurance of an ongoing pregnancy. Our results suggest that a combination of serum progesterone and HCG measurements provide clinically useful biochemical information which enhances the prediction of pregnancy outcome.

Chorionic Gonadotropin↗

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure.

BACKGROUND: Experimental renal failure causes structural alterations of the kidney. It is still unresolved how these changes are modified by antihypertensive treatment. Purpose of the study. To examine the effects of different antihypertensive agents (ramipril, nifedipine, moxonidine) mainly on glomerular geometry, cell number, cell morphology, and capillarization, in a subtotal nephrectomy model of renal failure. MATERIAL AND METHODS: Sham-operated male SD rats and subtotally nephrectomized (SNX) ad libitum-fed rats were examined. Groups of 8-10 SNX rats were left untreated or were treated with ramipril (0.5 mg/kg b.w. per day), nifedipine (20 mg/kg b.w. per day) or moxonidine (10 mg/kg b.w.per day) respectively. After perfusion fixation the kidneys were examined using stereological techniques. RESULTS: Systolic blood pressure (by tail plethysmography) was 110+/-13 mm Hg in sham-op and 119+/-9 in SNX. It was effectively and comparably reduced below normal values by ramipril (89+/-11 mmHg), nifedipine (98+/-23 mmHg) and moxonidine (92+/-11 mmHg). The glomerulosclerosis index (SI) was significantly increased in SNX versus sham-op; it was similarly decreased by ramipril and moxonidine but less so by nifedipine. Vascular damage (preglomerular vessels) was reduced by all treatments whereas tubulointerstitial damage was signficantly reduced only by ramipril and moxonidine. Mean glomerular tuft volume was increased in SNX compared to sham-op. controls and was normalized only by ramipril treatment. Glomerular cells were differentially affected the three antihypertensive agents. After subtotal nephrectomy an increase in podocyte volume and mesangial cell number per glomerulus was noted. Nifedipine, and to a lesser extent ramipril, prevented mesangial cell hyperplasia. In contrast, only the ACE inhibitor ramipril, but not nifedipine or moxonidine prevented podocyte abnormalities, particularly podocyte hypertrophy. CONCLUSIONS: (i) Despite comparable reduction in systolic blood pressure, different classes of antihypertensive agents had diverse effects on renal damage in subtotally nephrectomized rat. This observation is consistent with specific, non-hemodynamic actions of anti-hypertensives. (ii) Glomerular and tubulointerstitial damage are prevented by treatment with ACE inhibitors and antisympathotonic agents, but not with the calcium antagonist nifedipine. In contrast, renal vascular changes were also prevented by nifedipine. (iii) Only ACE inhibitors effectively inhibited podocyte hypertrophy and mesangial cell hyperplasia. Whether the superior effect of ACE inhibitors on glomerulosclerosis is related to inhibition of glomerular growth and podocyte hypertrophy as well as preservation of podocyte structure, or whether these findings are merely a passive reflection of greater efficacy, remains unresolved.

Animals↗

Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin.

OBJECTIVE: Iridocyclitis has been identified as a dosage-dependent side effect in patients with the acquired immunodeficiency syndrome (AIDS) who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. We reviewed cases of acute hypopyon uveitis occurring in patients with AIDS to establish whether there was an association. DESIGN: Retrospective case series. SETTING: Outpatient clinic and inpatient hospital-based ophthalmology referral practice and infectious disease specialty service. PATIENTS: Seven patients with AIDS, aged 10 to 40 years, presenting with acute unilateral hypopyon mimicking infectious endophthalmitis. MAIN OUTCOME MEASURES: Findings from complete ophthalmological evaluation and ancillary laboratory testing. RESULTS: At the time of presentation, all seven patients were receiving treatment for MAC infection with rifabutin (dosage range, 300 to 600 mg/d) and clarithromycin. Results of microbiological investigations in five patients were negative. Iridocyclitis became bilateral in all seven patients, and hypopyon developed in the contralateral eye in five of seven patients. Hypopyon resolved rapidly with intensive topical corticosteroid therapy. Residual inflammation responded to topical corticosteroids with or without reduction of the rifabutin dosage. CONCLUSIONS: Concomitant use of rifabutin, clarithromycin, and fluconazole may precipitate hypopyon uveitis in patients with AIDS being treated for MAC infection.

AIDS-Related Opportunistic Infections↗

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult↗

Clear cell neoplasm.

We are reporting four cases of clear cell neoplasm. Local infiltration and destruction was observed in one case while in a second case, originating in the sublingual gland, metastasis to the lymph nodes occurred. The behaviour of these neoplasms has prompted the suggestion that these tumours be designated carcinomas rather that noncommittally tumours or neoplasms (Batsakis and Regezzi, 1977). The histopathological characteristics of our four cases conform to those that have been articulated and believed to be the distinctive features of these tumours (Batsakis and Regezzi, 1977). It is hoped that ours and similar reports will be helpful towards clearing the diagnostic and taxonomic confusion regarding these tumours.

Adenocarcinoma↗

Ca2+ mobilization by the LH receptor expressed in Xenopus oocytes independent of 3',5'-cyclic adenosine monophosphate formation: evidence for parallel activation of two signaling pathways.

The cDNAs encoding the murine LH receptor (LHR) and the human beta 2-adrenoceptor (h beta 2AR) were cloned and RNAs complementary to their sense strands (cRNAs) were injected into defolliculated Xenopus oocytes. This led to expression, respectively, of LH- and isoproterenol-stimulable adenylyl cyclase activities, indicating that functionally active receptor cDNAs had been cloned. In oocytes injected with LHR cRNA, but not in control or h beta 2AR cRNA-injected oocytes, human CG and LH increased a Ca(2+)-activated Cl- current, as measured by the two-microelectrode voltage-clamp method. This effect was not seen with isoproterenol in control or h beta 2AR cRNA-injected oocytes, it was also not observed in response to forskolin or (Bu)2cAMP. The response to human CG could be obtained in the absence of extracellular Ca2+ but was abolished by injection of EGTA, indicating that it was caused by mobilization of Ca2+ from intracellular stores. The response was unaffected by overnight treatment with 1 microgram/ml pertussis toxin. The experiments show that a glycoprotein hormone receptor can be expressed as a functionally active molecule in Xenopus oocytes, and that the LHR has the ability of activating two separate intracellular signaling pathways: one forming the second messenger cAMP, and the other mobilizing Ca2+ from intracellular stores. It is proposed that the latter is secondary to a primary activation of phospholipase C by the LHR, which elevates intracellular Ca2+ via intermediary elevation of inositol phosphates, presumably (1,4,5)inositol trisphosphate.

Adenylyl Cyclases↗

Knowledge and beliefs about cancer in a socioeconomically disadvantaged population.

Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors.

Consumer Behavior↗

Treatment of refractory lymphoma with high dose cytarabine, cyclophosphamide and either TBI or VP-16 followed by autologous bone marrow transplantation.

This study was designed to test the efficacy and toxicity of combining high-dose cytarabine (3 g/m2 every 12 h x 8 doses day -7 to day -4, total dose 24 g/m2), methyl prednisolone (0.5 mg/kg every 4 h day -7 to day -1), and cyclophosphamide (CY) (60 mg/kg day -3 and day -2) with either total body irradiation (TBI) (900 cGy in a single fraction on day -1) or VP-16 (600 mg/m2/days -7, -5, and -3) in patients not eligible for TBI secondary to prior radiotherapy. We treated 14 patients (eight male, six female) with either non-Hodgkin's lymphoma (n = 5) or Hodgkin's disease (n = 9). All patients had failed prior conventional chemotherapy (median two regimens range 1-5). Five patients were treated with TBI and nine with VP-16. There were eight complete remissions, two partial remissions, four were inevaluable for response due to early death. Overall survival is 21% (3/14) and relapse-free survival is 7% (1/14) with the sole disease-free survivor now 40 months from transplant. Very significantly, among patients receiving TBI, there were no survivors (median survival 24 days, range 17-330 days) and 4/5 had pulmonary complications. Median DLCO in these four patients was 61% (range 50-67) prior to transplant and none had an infectious etiology established by bronchoalveolar lavage. Median time to an absolute granulocyte count of 500 x 10(6)/l was 16 days (range 10-37 days) and to a platelet count of 20 x 10(9)/l was 12 days (range 7-22 days). In conclusion, the addition of high-dose cytarabine (24 g/m2) to CY and single-dose TBI or VP-16, while being very active, produced excessive pulmonary toxicity in this group of patients with lymphoma.

Adolescent↗

Combined Kirschner-Ehmer device and dorsal spinal plate fixation technique for caudal lumbar vertebral fractures in dogs.

A new surgical technique was developed for the fixation of caudal lumbar vertebral fractures in dogs. The technique provides optimal stabilization, can be used in combination with dorsal decompression, and does not require an intact spinous process on the fractured vertebra or attachment of the fixation devices to the fractured vertebra. The fixation consists of a Kirschner-Ehmer device and dorsal spinal plates. After fracture healing, only mild sedation of the dog is needed to allow removal of the external hardware used in the fixation. The technique, its indications, and its use in 5 cases are described.

Animals↗

Combined Kirschner-Ehmer apparatus and dorsal spinal plate fixation of caudal lumbar fractures in dogs: biomechanical properties.

The strength and rigidity of a new surgical technique for the stabilization of caudal lumbar fractures in dogs, using a Kirschner-Ehmer apparatus and a dorsal spinal plate (KE/DSP), were compared with 2 other methods of internal spinal fixation and with intact (control) spines, using a spinal test system that subjected the spines to 4-point bending. The fixation devices were applied to isolated canine lumbosacral spines (L1 to S3) from cadavers. A complete spinal separation was made in the spine implant specimens at L5-L6 by sharp dissection of all ligamentous structures connecting the two vertebrae. Bending moment vs L5-L6 angular deformation curves, and rigidity and load sustained at 10 degrees angular deformation (failure) were recorded for each fixation method and for the control spines. Values were compared by statistical analysis. The combined KE/DSP fixation and a combined vertebral body plate/dorsal spinal plate (VBP/DSP) fixation were stronger and more rigid than were the control spines and those fixed with a modified segmental-fixation method (P less than 0.05). There were no statistical differences in strength and rigidity between the 2 combined-fixation techniques. Although the VBP/DSP technique is not applicable to clinical caudal lumbar (L5-L6) fractures, it was compared in this study to the KE/DSP technique because a similar VBP/DSP technique was reported strongest in a similar study of L3-L4 simulated fractures, compared with 3 other spinal-fixation techniques that have been used in repair of caudal lumbar fractures. The technique has been used successfully in 6 dogs with caudal lumbar fractures.

Animals↗

A case-control study of the association of sickle cell trait and chronic open-angle glaucoma.

Chronic open-angle glaucoma is reported to be more common in blacks than in whites. The reasons for a higher prevalence of this disease in blacks are unclear. Two recent small case series from clinical practice have been published in which secondary open-angle glaucoma was diagnosed in blacks with sickle cell trait who had experienced either traumatic or nontraumatic hyphema. The association of sickle cell trait and chronic open-angle glaucoma has been tested only in a small case-control study of uncontrolled chronic open-angle glaucoma patients undergoing surgery. No significant association was found. However, the higher prevalence of sickle cell trait in blacks compared with whites raises the question of whether the presence of sickle hemoglobin is a risk factor for chronic open-angle glaucoma in the black population. To test for a possible association between this disease and sickle cell trait, we conducted a case-control study in black ophthalmic patients at the University of Pennsylvania and affiliated hospitals between December 1981 and July 1982. Sickle cell trait, as measured by the sickle cell preparation test, was no more prevalent in patients with chronic open-angle glaucoma than in age- and sex-matched ophthalmic clinic controls. It is unlikely that hemoglobin SA is a risk factor for chronic open-angle glaucoma.

Adult↗